Study On The Correlation Between Inflammatory-Resolution Mediators LXA4 And RvD1 And Large Artery Atherosclerotic Stroke

Background:Large artery atherosclerotic(LAA)stroke is the most common subtype of ischemic stroke,and the key to prevent it is to control the pathophysiological process of atherosclerosis(AS)effectively.In essence,AS is a kind of chronic artery inflammation that is caused by uncontrolled inflammatory reaction and unbalance of lipid metabolism.For the chronic inflammation in AS lesions,most studies mainly focused on prevention and treatment strategies based on anti-inflammatory.Recently more and more researchers believe that although AS are caused by chronic inflammation triggered by pro-inflammation cytokines,the defective process of inflammatory regression mediated by inflammation-resolution mediators is the crucial reason for AS plaque progression and instability.Therefore,if we do not improve the regression of inflammation,it is never enough to delay or stop the progression and deterioration of plaque just through inhibiting inflammation.The process of inflammatory regression is regulated by pro-inflammatory regression mediators,including Resolvins(Rvs)、lipoxins(LXs)、protections(PDs)and maresins(Ma Rs).Animal experiments have found that lipoxin A4(LXA4)and Resolvin D1(RvD1)can reduce the degree of atherosclerosis in model mice.However,the correlation between inflammation-resolution factors and AS is less,the relationship between inflammation-resolution mediators and LAA cerebral infarction also needs us to explore.Purposes:By comparing the levels of inflammation-resolution mediators(LXA4、RvD1)combined with clinical features,imaging and laboratory findings in healthy、AS and LAA cerebral infarction patients to explore the correlation between LXA4 、RvD1 and the progression of AS and LAA cerebral infarction,thus providing new insights for the prevention and treatment of ischemic stroke.Methods:48 patients with acute large artery atherosclerotic stroke as group LAA and 41 patients with cerebral atherosclerosis rather than infarction as group AS.Both groups conformed to the inclusion criterias,and took cerebral vessel examination(color doppler ultrasound and CTA).According to the nature of atherosclerotic plaque,it can be divided into stable plaque subgroup and unstable plaque subgroup;and according to the degree of vascular stenosis,it can be divided into mild stenosis subgroup,moderate stenosis subgroup and severe stenosis subgroup.Patients in LAA group was divided into mild functional defect and moderate-severe functional defect subgroups according to NIHSS score standard questionnaire.In addition,18 healthy subjects were selected from the center of physical examination during the same period.Patients in group AS and group LAA received gathering fasting elbow venous blood within 24 hours after they were admitted to the hospital,29 patients in group LAA were extracted blood again 7 days from the onset.After centrifuging,ELISA was used to detect the level of LXA4、RvD1 in the serum.Through comparing the level of LXA4 、 RvD1,the condition of blood vessel,the NIHSS score and other releated information in three groups,to investigate the correlation between inflammationresolution factors LXA4、RvD1 and the occurrence and development of AS and LAA cerebral infarction.Results:1.There was no significant difference in gender,BMI,stroke history,coronary heart disease history,LDL,TC and TG between group contral、AS and LAA.The average age and proportion of hypertension in group AS were higher than those in group contral(P<0.05),There was no difference in diabetes/smoking history/drinking history、HDL、FBG between group control and AS(P>0.05).Compared with group contral,group LAA was higher in average age,proportion of hypertension/diabetes/smoking history、FBG,lower in HDL(P<0.05);there was no difference in proportion of drinking history between these two groups(P>0.05).Group LAA has higher proportion of smoking history/drinking history and FBG than group AS(P<0.05),and there was no difference in average age、proportion of hypertension history/diabetes history and HDL between these two groups(P>0.05).2.The level of LXA4 in group AS and group LAA was significantly lower than that in the group control(P<0.001),and there was no significant difference between group AS and the group LAA(P<0.05).There was no significant difference in the level of RvD1 between group control、AS and LAA(P>0.05).3.The levels of LXA4 and RvD1 in peripheral blood of some patients in group LAA were reexamined after 7 days from the onset.The results showed that the levels of LXA4 and RvD1 were lower than those at admission,and the difference was statistically significant(P<0.05).4.Subgroup analysis of plaque stability: The proportion of stable plaque and unstable plaque in group AS was 79.5% and 20.5% respectively,and that in group LAA was 54.2% and 45.8% respectively.The proportion of stable plaque in group AS was significantly higher than that in group LAA(79.5% > 54.2%,P< 0.05),and the proportion of unstable plaque in group AS was significantly lower than that in group LAA(20.5% < 45.8%,P < 0.05).The level of LXA4 in unstable plaque subgroup was significantly lower than that in stable plaque subgroup(P<0.05).There was no significant difference in the level of RvD1 between unstable plaque subgroup and stable plaque subgroup(P>0.05).5.Subgroup analysis of vascular stenosis showed that mild stenosis was dominant in group AS(51.2%),moderate and severe stenosis was dominant in group LAA(93.8%),with statistical significance(P<0.001).There was no significant difference in the levels of LXA4 and RvD1 among the subgroups with different degree of stenosis(P>0.05).6.Subgroup analysis of neurological deficit: there was no significant difference in LXA4 and RvD1 expression between the mild neurological deficit subgroup and the moderate-severe neurological deficit subgroup in patients with LAA cerebral infarction(P>0.05).Conclusions:1.The level of LXA4 in peripheral blood of patients with AS and LAA cerebral infarction decreased,and the level of LXA4 in peripheral blood of patients with unstable plaque decreased more significantly,suggesting that LXA4 is closely related to AS and LAA stroke,it may become a biomarker for AS and stroke risk prediction.2.The level of RvD1 in patients with AS and LAA stroke had no significant change.However,compared with the level of admission,patients with LAA stroke had much lower RvD1 in peripheral blood collected 7 days after the onset,suggesting that the change of RvD1 may be related to the progression of cerebral infarction,but it needs further study to confirm.